305. Human Leukocyte Antigen Association in Azathioprine-induced ug Hypersensitivity Reactions in Patients with Anti-Neutrophil-Cytoplasmic-Antibody Associated Vasculitis.

Background: ug hypersensitivity reactions (DHRs) account for 6-10% of all ug reactions and may be linked to specific human leukocyte antigen (HLA) genes, particularly class 1 HLA antigens. Azathioprine (AZA) is a therapeutic agent used in the management of Anti-Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis (AAV). Although infrequent, AZA induced DHRs can be life-threatening and have a reported incidence of up to 9% in AAV patients (1). Methods: We conducted a retrospective review on a cohort of AAV patients previously treated with, or currently on AZA maintenance therapy. Participants were categorised into those who had experienced AZA DHR and those who were AZA tolerant. High resolution HLA tissue typing was performed in both groups. The primary endpoint was identification of a HLA gene association with AZA DHRs in the context of AAV. Results: The class I HLA allele, HLA-C*06:02, was solely expressed in AZA DHR patients (33.3%), whilst no patient who tolerated AZA had this allele (0.0%). This yielded a positive predictive value of 100% for HLA-C*06:02 in predicting AZA DHR in AAV patients, negative predictive value of 66.7%, sensitivity of 33.3% and specificity of 100% (Table 1). Conclusion: HLA-C*06:02, a well-recognised susceptibility allele found in association with psoriasis (2), may predict the development of AZA-induced DHR in patients with AAV. Given the potentially life-threatening nature of such reactions, prospective screening for this HLA marker could be considered, with avoidance of AZA among those with HLA-C*06:02 and caution with AZA in those without the allele. Verification among a larger cohort of patients will be required to confirm this recommendation. Disclosures: None. References 1. Hessels AC, Sanders JSF, van de Ven A, Kroesen BJ, Lambeck AJA, Rutgers A, et al. Azathioprine Hypersensitivity Synome in a Cohort of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Patients. J Allergy Clin Immunol Pract. 2019;7(3):1004-9. 2. Chen L, Tsai TF. HLA-Cw6 and psoriasis. Br J Dermatol. 2018;178(4):854-62